The present invention relates generally to radioactive sources used for treatment of tissue in the human body. More particularly, the invention resides in a device, apparatus, and methods for treating tissue by irradiation with a predetermined dose from a radioactive source which is delivered into the body of the patient via a natural or artificial pathway for a very brief treatment interval or fractionated treatment sessions. The device, apparatus and methods of the invention are especially well suited for brachytherapy in which a malignant tumor is exposed to localized in vivo radiation from a pathway within or adjacent the tumor site, or for controlled irradiation of the wall of a blood vessel, particularly coronary arteries or related blood-carrying canals, to condition the interior surface thereof against restenosis.
Brachytherapy, a technique for radiation treatment of malignant tumors, attacks the tumor from within the body. The method typically utilizes a radioactive source wire in which a radioisotope sealed at and substantially integral with the distal tip of a relatively thin wire or cable is delivered via a pathway formed by a catheter or through a natural cavity, duct or vessel of the body directly to the tumor site for localized irradiation. One or more catheters, for example, may be implanted in the patient's body to provide the pathway(s) from a point external to the body to and through the tumor site, so that the interior of the tumor mass is accessible via the catheter(s). The radioactive source, with a radioactivity and that may range from about one curie to about ten curies, is mechanically delivered to the site either by hand feeding the source wire (for low dose and more readily accessible tumor sites) or by means of apparatus known as an afterloader which has a drive system to which the proximal end of the source wire is connected.
Usually, the treatment is fractionated, in that repeated short intervals of treatment are performed, with the source wire being introduced for the irradiation, left in place for the predetermined interval prescribed by the attending oncologist (often after consultation with a physicist who has calculated the size of the tumor, the distance to be traveled by the source, the nature of the pathway to be traversed and likely travel time, and other pertinent factors), and then withdrawn into the afterloader's shielded safe. To permit treatment to be performed through multiple catheters to the tumor site, if deemed appropriate by the oncologist, the afterloader may be provided with a turret for automatic delivery of the source wire in succession to the entry points of the several catheters for automated advancement, treatment and withdrawal in each pathway. The desired treatment time in each case is programmed into the afterloader's control unit.
The treatment regimen may be repeated at regular intervals over a period of many days, weeks or months, and, if successful, results in complete destruction or at considerable shrinkage of the tumor(s). Among the advantages of this type of radiation therapy are exposure of the tumor to fractionated treatment doses of localized radiation so that each individual treatment need only be of extremely short duration to provide the desired effect while reducing the extent of patient exposure and discomfort, and to provide relatively rapid shrinking of the tumor while avoiding prolonged exposure of healthy tissue to radiation.
Because this type of therapy is more applicable to inoperable malignancies deep within the body, the site of the tumor(s) is usually difficult to reach as the source wire is guided through the path provided by the implanted catheter. The catheter itself may be positioned in place using a previously implanted guidewire or "rail" over which it is advanced along a lumen distinct from the lumen of the catheter through which the source wire is advanced and retracted. It is often the case that this pathway is long, extremely narrow and tortuous with numerous bends and turns. It is essential, therefore, that the source wire should be suitably thin, strong and flexible to traverse the pathway. Furthermore, the wire must be adapted to carry a suitably sized radioactive source, i.e., the core which, for high dosage treatments, is typically substantially pure iridium processed in a neutron flux to produce the radioactive isotope Ir-192. Hence, the source wire has the conflicting requirements that it be of sufficiently small diameter and flexibility to traverse the path to and from the tumor, sufficiently strong along with its flexibility to be driven through the pathway without binding or kinking during wire advancement, and with the capacity to deliver a radiation dosage of as much as ten or more curies.
Prior art source wires include cable composed of a multiplicity of tiny strands of stainless steel wire to provide both desired strength and flexibility, but which lack the size or diameter to travel through the smallest sizes of pathways required for brachytherapy treatment of certain tumors, such as in or through the biliary tract or the bronchi of the lungs. Also, cable source wires typically require welding a plug or capsule containing the radioactive source to the distal tip, which creates a point of weakness where fracture may occur. It is imperative, of course, that the source wire be sufficiently sound and reliable to avoid even the remote possibility that it may break and cause the radioactive material portion to be left in the patient's body for a protracted interval of time.
A solid source wire is capable of accommodating the Ir-192 or other source material in a hole formed in the distal tip of the wire to provide better sealing and security of the source material. Also, solid source wire can be produced by specialized techniques in sizes ranging down to from about 0.6 to 0.7 millimeter (mm) diameter to accommodate an Ir-192 source having a dosage or radioactive level or strength of up to about 10 curies. Other conventional source materials include cobalt, cesium, palladium, gold, and iodine. The source wire may be composed of stainless steel, platinum or certain other conventional materials of suitable flexibility.
For low dose sources in particular, such as one curie or slightly higher, the source material may be installed and the entire source wire then subjected to processing in a nuclear reactor to impart the desired level of radioactivity to the source material. This is an acceptable procedure where the half-life of the wire material is considerably less than that of the source material, so that the radioactivity of the wire material itself is sufficiently dissipated to permit it to be used within a few days after activation. Platinum wire, for example, is suitable for that purpose. For higher dose sources, the source material alone is subjected to the neutron flux and subsequently assembled in the wire by means of shielded, remotely controlled handling and manipulating techniques.
Recently, it has been found that radioactive irradiation of the interior wall surface of blood vessels in general and the coronary arteries in particular with a low dose source for a very brief interval following treatment of the vessel for removal or compression of occluding, lagging, or lacking material such as plaque, enjoys marked success in preventing restenosis. Restenosis is a recurrence of the stricture or narrowing of the vascular lumen or heart valve following surgery or other treatment for removal or reduction of an occlusion, or from related trauma. For example, cardiac patients who have been treated by balloon angioplasty, artery interior wall scraping, laser removal of plaque, by-pass surgery, and other conventional techniques for treating stenosis or occlusion of the blood vessels either because of or in avoidance of myocardial infarction, have been found to experience high incidence of restenosis.
Approximately one-third of the patients who have had arteries unblocked suffer restenosis about six months later, requiring that the procedure be redone. And in fact, repeating the procedure appears to increase the trauma to the smooth muscle cells and to speed their regrowth. Fifty percent of the patients experience some form of re-occlusion of the treated vessel. While a repeat procedure may not be required for all of those patients, some re-occlusion does occur. The remaining 50% of the patients seem to suffer no re-occlusion, and there is no single explanation for it.
The fact that one-third of all patients require re-treatment, at substantial additional cost and with potential loss of life raises questions concerning the significance of a 95% success rate for the initial unblocking procedure. Moreover, if a second re-occlusion occurs, the next procedure performed on the patient is likely to be open heart surgery.
Restenosis, then, is really an injury response mechanism to the unblocking procedure, at least for some substantial percentage of the patients. Attempts to correct the restenosis problem by use of drugs have not been successful.
Irradiation of the vessel wall with a radioactive source appears to alleviate the problem in tests conducted on rabbits and rats, but creates a new problem in that the source wire must be sufficiently thin, flexible and strong to be capable of placement in the offending arteries. This is by no means a simple task, because of the small size of the vessels, the difficulty in reaching the target area through the artery as a consequence of the small size of the target and the tortuous pathway involved, and especially the susceptibility of the patient to a heart attack if the critical vessel is blocked for an inordinate time during performance of the treatment.
The problems involved are similar to, if not greater than, those encountered in treatment of tumors by brachytherapy as described above. It is a principal object of the present invention to provide new and improved source wires, apparatus and methods for in vivo, localized, internal radioactive treatment of selected tissue in the human body.
The cost of treatment for heart attack victims is staggering, and is among the procedures being addressed in a strong effort toward cost containment by treatment centers and other care providers. Of course, if treatment is unsuccessful, inadequate or untimely, the cost is even greater--in loss of life. Therefore, it is another important object of the present invention to provide improved and lower cost means and methods for treating cardiac patients to avoid restenosis of the veins and arteries, and even of the heart valves, following procedures used to open a blocked or partially blocked or inoperative blood passageway.